title: Hepatitis C virus RNA replication in human stellate cells regulates gene expression of extracellular matrix-related molecules.
abstract: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, including chronic hepatitis, fibrosis, and cirrhosis. Fibrosis often develops in HCV-infected livers and ultimately leads to cirrhosis and carcinoma. During fibrosis, hepatic stellate cells (HSC) play important roles in the control of extracellular matrix synthesis and degradation in fibrotic livers. In this study, we established a subgenomic replicon (SGR) cell line with human hepatic stellate cells to investigate the effect of HCV RNA replication on HSC. Isolated SGR clones contained HCV RNA copy numbers ranging from 10(4) to 10(7) per μg total RNA, and long-term culture of low-copy number SGR clones resulted in markedly increased HCV RNA copy numbers. Furthermore, HCV RNA replication affected gene expression of extracellular matrix-related molecules in both hepatic stellate cells and hepatic cells, suggesting that HCV RNA replication and/or HCV proteins directly contribute to liver fibrosis. The HCV RNA-replicating hepatic stellate cell line isolated in this study will be useful for investigating hepatic stellate cell functions and HCV replication machinery.
authors.affiliation: Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Watanabe
authors.forename: Hideki
authors.initials: H
authors.lastname: Aizaki
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Matsuura
authors.forename: Soichi
authors.initials: S
authors.lastname: Kojima
authors.forename: Takaji
authors.initials: T
authors.lastname: Wakita
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D016326:Extracellular Matrix Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000502:physiology*; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000821:virology*; D006526:Hepatitis C / Q000235:genetics* / Q000821:virology*; D006801:Humans; D012367:RNA, Viral / Q000096:biosynthesis; D017361:Viral Nonstructural Proteins / Q000096:biosynthesis / Q000235:genetics; D014779:Virus Replication
chemical_list: D016326:Extracellular Matrix Proteins; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins